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原发性脑胶质瘤中 TERT C228T 突变与 MALAT1 失调的共存:新的预后和治疗靶点。

Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets.

机构信息

Inegol Vocation School, Bursa Uludag University, Bursa, Turkey.

Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.

出版信息

Neurol Res. 2021 Nov;43(11):916-925. doi: 10.1080/01616412.2021.1948738. Epub 2021 Jul 1.

DOI:10.1080/01616412.2021.1948738
PMID:34210246
Abstract

: This study was designed to conduct molecular classification based on , and changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. We analyzed the expression profiles of and MALAT1 using the qRT-PCR method and and mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. mutation was observed in 5 (5.88%) and mutation in 65 (76.47%) primary pediatric and adult GB patients. and were detected in 18 (21.18%) and 7 (8.24%) patients. mutation and loss of were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Our findings highlight that the presence of C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

摘要

本研究旨在对儿科和成人原发性胶质母细胞瘤(GB)进行基于 和 变化的分子分类,并分析确定的同质亚组中 LncRNA MALAT1 的潜在相互作用。我们使用 qRT-PCR 方法分析了 85 例原发性儿科和成人 GB 患者的 和 MALAT1 的表达谱,并通过 DNA 测序分析检测了 和 突变状态。在 5(5.88%)例和 65(76.47%)例原发性儿科和成人 GB 患者中观察到 突变和 突变。在 18(21.18%)例和 7(8.24%)例患者中检测到 和 。 突变和 的缺失与总生存期短相关(p<0.001,p<0.001)。携带特别是 C228T 突变的患者预后更差(p<0.001)。从遗传分析中获得了 6 个亚组。在亚组中,与 D 组和 E 组相比,仅携带 突变的 A 组 MALAT1 表达更高(p=0.001 和 p<0.001);此外,C228T 突变患者中 MALAT1 高表达与预后不良相关(p<0.001)。我们的研究结果强调,存在 C228T 突变和 MALAT1 的表达可以作为原发性 GB 患者随访和新治疗策略开发的主要目标。

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